地顶胞霉菌丝体对酒精诱导小鼠急性肝损伤的保护作用

目的研究地顶胞霉菌丝体(AMM)对酒精所致小鼠急性肝损伤的保护作用。方法采用酒精灌胃造成小鼠急性酒精性肝损伤模型,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性和肝脏匀浆中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量,HE染色观察AMM对酒精小鼠肝脏形态学影响。结果 AMM(1 000 mg.kg-1、500 mg.kg-1)可降低血清中ALT、AST活性及肝组织中MDA的含量;升高肝组织匀浆中SOD的活性;HE染色结果显示AMM能明显减轻肝脏的病理损伤。结论 AMM对酒精所致小鼠急性肝损伤模型具有一定的保护作用。     

南沙参多糖对小鼠CCl4急性肝损伤的保护作用

目的探讨南沙参多糖(RAPS)对肝损伤的保护作用.方法采用四氯化碳(CCl4)诱导小鼠急性肝损伤模型,测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性、肝匀浆中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,观察肝组织病理学改变.结果RAPS各剂量组(2000,1000,500 mg·kg-1)不仅能显著降低肝损伤小鼠血清AST、ALT活性,而且能够降低肝损伤小鼠肝组织MDA含量,并能提高SOD活性;病理形态学观察显示,RAPS能够明显减轻肝细胞肿胀、减少中性粒细胞浸润,其对急性肝损伤具有治疗作用.结论RAPS对CCl4诱导的急性肝损伤具有显著的保护作用,该保护作用可能与其抗氧化作用有关.     

壳寡糖对四氯化碳致急性肝损伤小鼠的保护作用

目的研究壳寡糖对四氯化碳(CCl4)诱导的化学性肝损伤小鼠的保护作用。方法小鼠随机分组,连续7d灌胃给予50,167,500mg.kg-1.d-1壳寡糖,于第7天腹腔注射四氯化碳制备小鼠急性肝损伤模型,检测血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性;测定肝组织中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性;采用光学显微镜观察肝脏组织形态学变化。结果中、高剂量的壳寡糖能明显抑制肝损伤小鼠血清ALT和AST活性的升高(P<0.05),抑制肝组织中MDA含量的升高(P<0.01),提高肝组织中SOD的活力(P<0.05),减轻CCl4对肝脏细胞的病理损伤。结论壳寡糖对四氯化碳造成的小鼠急性肝损伤具有一定的保护作用。     

舒肝安乐宁浸膏对小鼠急性酒精性肝损伤保护作用的研究

目的研究舒肝安乐宁浸膏对小鼠急性酒精性肝损伤的保护作用。方法以白酒灌胃法建立小鼠急性酒精性肝损伤模型,观察血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、甘油三酯(TG)指标的变化,并进行病理组织学检测。结果各剂量舒肝安乐宁浸膏能显著降低小鼠血清ALT、AST活性和肝组织MDA、TG含量(P<0.05或P<0.01),提高肝组织SOD活性,减轻肝脏的病理损伤。结论舒肝安乐宁浸膏对急性酒精性肝损伤有保护作用。其作用机制可能为减少自由基的产生,抑制脂质过氧化反应,减少脂肪在肝脏的沉积。     

肝复康胶囊对四氯化碳所致小鼠肝损伤的保护作用

目的 研究肝复康胶囊对四氯化碳(CCl4)所致小鼠肝损伤的保护作用.方法 将肝复康胶囊灌胃给予小鼠,腹腔注射四氯化碳所致肝损伤小鼠,用半自动生化分析仪测小鼠血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性,以比色分析法测定肝匀浆丙二醛(MDA)含量及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性.结果 肝复康胶囊(0.9、1.8、3.6 g·kg-1·d-1)均可显著降低四氯化碳致肝损伤小鼠血清ALT和AST活性,也能明显降低肝脏MDA含量和提高肝匀浆SOD和GSH-Px活性.结论 肝复康胶囊对小鼠急性肝损伤有一定保护作用,其保护作用机制可能与清除自由基,抗脂质过氧化作用有关.     

灯盏乙素对异烟肼和利福平合用致小鼠肝损伤的保护作用

目的:观察灯盏乙素对异烟肼(INH)和利福平(RFP)合用致小鼠肝损伤的保护作用.方法:小鼠每天同时灌胃RFP和INH各100 mg·kg-1,2 h后灌胃灯盏乙素50,100,200 mg·kg-1,qd,连续给药10 d,末次给药16 h后,取血和各器官组织,测定肝、脾和胸腺指数、血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性、肝匀浆中超氧化物歧化酶(SOD)、脂质过氧化物丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)以及一氧化氮(NO)的含量.结果:灯盏乙素能显著降低RFP和INH合用致肝损伤小鼠的肝指数、血清ALT和AST活性、肝匀浆中的MDA和NO含量,并能显著提高肝匀浆中的SOD和GSH-Px活性.结论:灯盏乙素对RFP和INH合用致小鼠肝损伤具有明显的保护作用,可能与其抗脂质过氧化及调节体内NO水平有关.     

荞麦花叶芦丁对糖尿病大鼠早期肝损伤的保护作用

目的 观察养麦花叶芦丁(RBFL)对糖尿病大鼠早期肝损伤的保护作用.方法 采用四氧嘧啶加脂肪乳诱导大鼠糖尿病模型.实验分正常对照组(A组)、模型组(B组)、RBFL干预组(C组)[成模后灌胃RBFL,低剂量(Ch1组)25 mg·kg-1·d-1、中剂量(C2组)50 mg·kg-1·d-1、高剂量(C3组)100nag·kg-1·d-1]和阳性药物对照组(D组)(成模后灌胃罗格列酮3 mg·kg-1·d-1),每组10只.观察RBFL对糖尿病大鼠空腹血糖(FBG)、血清Tbil、ALT、肝脏系数(LI)及肝组织形态学改变的影响.结果 C组FBG在用药1～4周内有增加趋势,但增加的速度和幅度较B组低;C2、C3组在6周后与B组差异显著(P<0.05,P<0.01).与B组比较,C组血清Tbil、ALT升高幅度更低(P<0.05),C3组LI明显下降(P<0.05).镜下C组肝细胞形态基本恢复.结论 RBFL对糖尿病大鼠早期肝脏损伤具有一定的保护作用.     

白首乌C21甾体酯苷对小鼠急性四氯化碳肝损伤的保护作用

目的 研究白首乌C21甾体酯苷对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用.方法 以CCl4灌胃(ig.)小鼠制备急性肝损伤模型.测定血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的活性、肝组织中超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量,并做肝脏形态组织学观察.结果 白首乌C21甾体酯苷高、中、低剂量(40、20、10 mg·kg-1·d-1)均能明显抑制肝损伤小鼠血清中ALT和AST活性(P＜0.01)及肝组织中MDA含量的升高(P＜0.05),增强SOD活力(P＜0.05),减轻肝细胞的损伤程度.结论 白首乌C21甾体酯苷对CCl4引起的小鼠急性肝损伤具有保护作用,其机制可能与抗脂质过氧化有关.     

老鹳草提取物对小鼠免疫性肝损伤的保护作用

目的:考察老鹳草提取物对免疫性肝损伤小鼠的保护作用。方法:分别采用卡介苗(BCG)+脂多糖(LPS)、刀豆蛋白A(ConA)诱导建立小鼠免疫性肝损伤模型,灌胃给予老鹳草提取物(100,200,400mg.kg-1),观察小鼠血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和乳酸脱氢酶(LDH)的活性及血清总蛋白(TP)、白蛋白(ALB)、细胞因子γ干扰素(IFN-γ)和白细胞介素4(IL-4)含量变化;检测肝组织匀浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;进行肝脏病理组织检查。结果:不同剂量老鹳草提取物均可明显降低小鼠血清中AST,ALT活性及肝组织匀浆MDA含量(P<0.05或0.01),并能使降低的SOD活性升高;中、高剂量老鹳草提取物(200,400 mg.kg-1)可不同程度降低血清中IFN-γ和IL-4含量及LDH活性(P<0.05)。不同剂量老鹳草提取物可使血清蛋白含量维持正常比例,肝组织损伤均有不同程度减轻。结论:老鹳草提取物对小鼠免疫性肝损伤具有一定的保护作用。     

竹节参提取物对小鼠急性酒精性肝损伤的保护作用

目的:研究竹节参60％乙醇提取物对小鼠急性酒精性肝损伤的保护作用.方法:将40只昆明种小鼠随机分为正常组、模型组、竹节参提取物高剂量组、竹节参提取物低剂量组、水飞蓟宾组;采用白酒灌胃的方式建立小鼠急性酒精性肝损伤模型.测定各组小鼠ALT、AST、TG含量水平,以及肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)含量,光学显微镜观察小鼠肝脏病理变化,PCR技术检测SOD1和GPX1基因表达水平.结果:与正常组相比较,模型组小鼠肝脏出现明显脂肪变性,血清ALT、AST和TG的水平升高,肝脏SOD和GSH-Px活性明显降低,同时MDA含量显著升高,差异具有统计学意义(P＜0.05或P＜0.01);与模型组相比,竹节参提取物高、低剂量组和水飞蓟宾组均可降低ALT、AST和TG的含量;升高肝脏SOD和GSH-Px活性,同时降低MDA的含量;并且肝组织SOD1和GPX1基因的表达水平明显上调,差异具有统计学意义(P＜0.05或P＜0.01).结论:竹节参提取物对小鼠急性酒精性肝损伤有明显的保护作用,其机制可能是通过上调SOD1和GPX1的基因表达,从而减轻酒精诱导的氧化应激对肝脏的损伤.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.